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Early growth is associated with future metabolic risk; however, little is known of the underlying biological pathways. In this prospective study of 249 boys and 227 girls, we sought to identify sex-specific metabolite profiles that mark the relationship between age and magnitude of the infancy body mass index (BMI) peak, and the childhood BMI rebound with a metabolic syndrome z-score (MetS z-score) during early adolescence (median age 12.8 years). Thirteen consensus metabolite networks were generated between male and female adolescents using weighted correlation network analysis. In girls, none of the networks were related to BMI milestones after false discovery rate (FDR) correction at 5%. In boys, age and/or magnitude of BMI at rebound were associated with three metabolite eigenvector (ME) networks comprising androgen hormones (ME7), lysophospholipids (ME8), and diacylglycerols (ME11) after FDR correction. These networks were also associated with MetS z-score in boys after accounting for age and race/ethnicity: ME7 (1.43 [95% CI: 0.52, 2.34] units higher MetS z-score per 1 unit of ME7), ME8 (-1.01 [95% CI: -1.96, -0.07]), and ME11 (2.88 [95% CI: 2.06, 3.70]). These findings suggest that alterations in sex steroid hormone and lipid metabolism are involved in the relationship of early growth with future metabolic risk in males.

Metabolite Profiles of the Relationship between Body Mass Index (BMI) Milestones and Metabolic Risk during Early Adolescence